Multidisciplinary care with deep brain stimulation for Parkinson’s disease patients

Hong Kong Med J 2014 Dec;20(6):472–3
DOI: 10.12809/hkmj144426
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
EDITORIAL
Multidisciplinary care with deep brain stimulation for Parkinson’s disease patients
YF Cheung
Department of Medicine, Queen Elizabeth Hospital, Hong Kong; Hong Kong Movement Disorder Society
 
Corresponding author: Dr YF Cheung (cyfz02@ha.org.hk)
 
 Full paper in PDF
Since Benabid et al’s introduction in 1987,1 deep brain stimulation (DBS) has emerged as a standard therapeutic option for various movement disorders when they become refractory to pharmacological treatment. The commonest clinical indications for DBS include Parkinson’s disease (PD), dystonia, and essential tremor.2 3 In Hong Kong, more than 200 patients have received DBS therapy since 1997 when the procedure was first introduced to Hong Kong. Apart from PD, which accounts for most patients,4 5 successful treatment has been reported locally in patients with dystonia6 and Tourette’s syndrome.7 Deep brain stimulation devices are expensive. In the Hospital Authority, these devices for advanced PD and severe dystonia are covered under standard services for improving the standard of care, provided that certain selection criteria have been fulfilled. This programme has facilitated provision of DBS services to those patients in need, but who cannot afford the devices themselves.
 
In this issue of the Hong Kong Medical Journal, the Prince of Wales Hospital/Chinese University of Hong Kong Movement Disorder Group5 report their experience of 41 PD patients who received bilateral subthalamic nucleus DBS over 12 years. The group has demonstrated both efficacy and safety of the procedure by improvement of Unified Parkinson’s Disease Rating Scale part II and III scores of 32.5% and 31.5%, respectively and improvement in PD diary parameters, as well as its low surgical complication rate and zero perioperative mortality.
 
The authors5 also compared the outcomes of patients operated on before mid-2005 with those operated on after that date, and showed significant improvement in the latter group. They attributed the difference to multiple factors, one of which is the dedicated, multidisciplinary approach that they adopted. Deep brain stimulation is a procedure that emphasises multidisciplinary teamwork. Expertise from various disciplines contributes to patient management, including neurologists, neurosurgeons, nurse specialists, clinical psychologists, radiologists, physiotherapists, occupational therapists, and speech therapists. Each team member has a specific role to play, yet coordination and communication between disciplines is key to the best outcome.
 
From a patient journey perspective, PD patients are first assessed by neurologists who check for the indications and contra-indications for DBS (eg does the patient really have advanced PD? Are there any physical or psychiatric illnesses that might increase the risks and adversely affect the outcomes?). Neurosurgeons determine whether a patient is a suitable surgical candidate and evaluate the surgical risks. Nurse specialists act as case managers to liaise with different parties and offer education and counselling to patients and their caregivers. Meticulous preoperative assessment is then performed, which is protocol-driven and includes detailed neuropsychological tests by clinical psychologists, magnetic resonance imaging of the brain by radiologists, and levodopa challenge test and video recording by neurologists and nurse specialists.
 
On the day of DBS, both the neurosurgeons and the radiologists are responsible for precise target localisation and trajectory planning. After the burr hole is created under local anaesthesia, microelectrode recording is performed by neurologists, who verify characteristic neuronal signals from the brain target. Once the quadripolar DBS electrode has been implanted, macrostimulation can be delivered and neurologists can assess the therapeutic responses and the thresholds for inducing side-effects. When the electrodes are optimally placed, an impulse generator is inserted under general anaesthesia by neurosurgeons. During the operation, nurse specialists play an important role in patient reassurance and alleviation of their anxiety.
 
Postoperative stimulation and DBS programming is usually delayed for a few weeks to allow for the microlesioning effects to resolve. Regular adjustment of pulse generator settings is performed by neurologists and nurse specialists to sustain clinical improvement, which can last for years. Rehabilitation is contributed to by physiotherapists, occupational therapists, and speech therapists. Ad-hoc troubleshooting is provided by nurse specialists. Finally, multidisciplinary clinics co-attended by clinicians, nurses, and allied health care professionals can enhance communication, care coordination, and patient accessibility.
 
The concept of multidisciplinary care in PD has evolved over many years. Parkinson’s disease is a heterogeneous condition, with both motor and non-motor manifestations, which vary considerably from one individual to another. As the disease progresses, new symptoms emerge that are levodopa-resistant and become the dominant causes of death and disability.8 9 Modern health care also underscores patient-centred care and patient empowerment, which highlights patient preferences and their own decision-making. Hence, it is generally accepted that a multidisciplinary health care model is preferable to a monodisciplinary model. In a recent review, van der Marck and Bloem10 have pointed out the challenges associated with the implementation of multidisciplinary care in PD. Due to the lack of high-quality conclusive evidence, the optimal composition of the team and the relative contribution of specialists remain unknown. The degree of collaboration between team members (ie multidisciplinary care, interdisciplinary care, or integrative care) that can translate into the most robust benefits is still unclear. It is also uncertain at what stage of the disease the application of an organised team approach can yield the best results. Finally, the setting of service delivery varies from centre to centre (ie in-patient, specialised out-patient centre, or regional community-based network).
 
Despite the challenges and the uncertainties mentioned above, multidisciplinary care will continue to be one of the pillars in the management of DBS patients. According to a survey in The Netherlands, barriers that impede the implementation of multidisciplinary care for PD include insufficient expertise, poor interdisciplinary collaboration, inadequate communication, and lack of financial support.11 We are probably facing similar problems in Hong Kong. While we wait for more evidence, efforts should be made in our local centres to develop rehabilitation protocols, provide training for movement disorder specialists, functional neurosurgeons, nurse specialists and allied health care professionals, and optimise delivery of DBS service in a streamlined and well-coordinated fashion.
 
References
1. Benabid AL, Pollak P, Louveau A, Henry S, de Rougemont J. Combined (thalamotomy and stimulation) stereotactic surgery for the VIM thalamic nucleus for bilateral Parkinson disease. Appl Neurophysiol 1987;50:344-6.
2. Okun MS. Deep-brain stimulation for Parkinson’s disease. N Engl J Med 2012;367:1529-38. CrossRef
3. Machado AG, Deogaonkar M, Cooper S. Deep brain stimulation for movement disorders: patient selection and technical options. Cleve Clin J Med 2012;79 Suppl 2:S19-24. CrossRef
4. Cheung YF, Chan HF, Poon TL, et al. The efficacy of deep brain stimulation for advanced Parkinson’s disease. Hong Kong Med J 2011;17 Suppl 5:S5.
5. Movement Disorder Group; Chan AY, Yeung JH, Mok VC, et al. Subthalamic nucleus deep brain stimulation for Parkinson’s disease: evidence for effectiveness and limitations from 12 years’ experience. Hong Kong Med J 2014;20:474-80.
6. Woo PY, Chan D, Zhu XL, et al. Pallidal deep brain stimulation: an effective treatment in Chinese patients with tardive dystonia. Hong Kong Med J 2014;20:455-9. CrossRef
7. Lee MW, Au-Yeung MM, Hung KN, Wong CK. Deep brain stimulation in a Chinese Tourette’s syndrome patient. Hong Kong Med J 2011;17:147-50.
8. Auyeung M, Tsoi TH, Mok V, et al. Ten year survival and outcomes in a prospective cohort of new onset Chinese Parkinson’s disease patients. J Neurol Neurosurg Psychiatry 2012;83:607-11. CrossRef
9. Hely MA, Morris JG, Reid WG, Trafficante R. Sydney Multicenter Study of Parkinson’s disease: non-L-dopa-responsive problems dominate at 15 years. Mov Disord 2005;20:190-9. CrossRef
10. van der Marck MA, Bloem BR. How to organize multispecialty care for patients with Parkinson’s disease. Parkinsonism Relat Disord 2014;20 Suppl 1:S167-73. CrossRef
11. Post B, van der Eijk M, Munneke M, Bloem BR. Multidisciplinary care for Parkinson’s disease: not if, but how! Postgrad Med J 2011;87:575-8. CrossRef

Evolving standards in preoperative staging and treatment of rectal cancer

Hong Kong Med J 2014 Oct;20(5):364–5
DOI: 10.12809/hkmj144370
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
EDITORIAL
Evolving standards in preoperative staging and treatment of rectal cancer
Jensen TC Poon, FCSHK, FHKAM (Surgery)
Division of Colorectal Surgery, Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong
 
Corresponding author: Dr Jensen TC Poon (jp@hkma.org)
 
 Full paper in PDF
Colorectal cancer has become the commonest cancer in Hong Kong since 2011 and rectal cancer constitutes about one third of all colorectal cancers.1 Rectal cancer has a much higher local recurrence rate of about 10% than colon cancer.2 Hence, stern efforts must be made to safeguard patients from recurrence during the management of rectal cancer. In current practice, good oncological outcome with low local recurrence rate for rectal cancer treatment relies on careful exercise of total mesorectal excision (TME) technique which is the standard for mid- and low-rectal cancer resection3 and perioperative radiotherapy with/without chemotherapy.
 
In the Dutch rectal cancer trial, combination of TME and preoperative short-course radiotherapy (5 Gy for 5 days) was associated with a significantly lower recurrence rate of 2.4% at 2 years versus 8.2% with TME only (P<0.001).4 A combination of long-course radiotherapy (usually 50.4 Gy over 6 weeks) and fluorouracil offers additional benefit of tumour downstaging to improve sphincter preservation rate or even complete tumour remission in about 15% to 20% of patients.5 Radiotherapy, given after operation, can also reduce local recurrence rate. However, a randomised trial showed that, compared with postoperative chemoradiation, preoperative chemoradiation was associated with significantly better local control and less toxicity for locally advanced rectal cancer, which is defined as T3 or T4 or lymph node–positive rectal cancer.6 Hence, most colorectal centres adopt the policy of offering neoadjuvant (preoperative) chemoradiation to locally advanced rectal cancer.
 
As the preoperative local staging of rectal cancer affects the management plan, the accuracy of staging is very important. Preoperative local staging usually relies on endorectal ultrasound or magnetic resonance imaging (MRI). Recently, MRI has emerged as the preferred modality for local staging of rectal cancer by colorectal surgeons. Apart from having high reproducibility and accuracy in assessing T stage and regional lymph node status, high-resolution MRI can predict circumferential resection margin (CRM) of the rectal tumour. In pathology terms, a positive CRM is defined as presence of tumour within 1 mm of radial surgical margin and it is associated with high chance of local recurrence. High-resolution MRI can accurately measure the closest distance between the tumour and mesorectal fascia and, hence, predict CRM. In a multicentre European trial (the MERCURY study), assessment of CRM by MRI was shown to be superior to TMN-based criteria in predicting local recurrence. After multivariate analysis, CRM was the only parameter that predicted local recurrence and patient survival in the preoperative stage.7 This finding suggested that MRI-predicted CRM assessment should be routinely incorporated into preoperative planning of rectal cancer treatment. The MERCURY study group proposed that the treatment plan of stage I to III rectal cancer can be guided by MRI assessment of rectal tumour.8 Good tumour prognosis by MRI is defined as predicted CRM of <1 mm, T1, T2 or T3 disease with depth of invasion of < 5 mm beyond muscularis propria (T3a/b), irrespective of regional lymph node stage. Poor tumour prognosis by MRI is defined as predicted CRM of <1 mm or T3 disease with depth of invasion of >5 mm beyond muscularis propria (T3c/d) or presence of extramural venous invasion. The centres involved in the MERCURY study had the policy of offering upfront surgery to tumours showing good prognosis by MRI and neoadjuvant chemoradiation to the tumours showing poor prognosis by MRI. The MERCURY study recorded local recurrence rate of only 3% in the tumours showing good prognosis by MRI and suggested omitting preoperative treatment in some stage III tumours. If the favourable results of the MERCURY study can be reproduced in other clinical trials, the MRI-predicted tumour prognosis system may become a new standard for deciding preoperative treatment of rectal cancer. However, the prerequisite for the success of a more selective approach in preoperative therapy is good TME technique by colorectal surgeons to avoid breaching of mesorectal fascia which may, otherwise, result in spillage of tumour cells and, subsequently, local recurrence. This is a serious concern when the tumour is covered and protected from exposure by only a few millimetres of CRM.
 
In the current issue of our journal, Wong et al9 report that the thickness of mesorectum in the Chinese is relatively thin and less than 15 mm in the majority of patients at most levels. As a result, the distance between the tumour and mesorectal fascia is intrinsically short. The CRM in Chinese patients with rectal cancer is reduced and, hence, more patients may have CRM which is involved or threatened by the tumour. This is a small series with only 25 patients and there is no similar report involving different ethnic groups for us to compare and ascertain if the mesorectum of the Chinese is thinner than that in patients of other ethnicities. However, we know that ultra-low rectal cancer (tumour within 5 cm from the anal verge) has a worse prognosis than higher tumour because the mesorectum tapers and thins out as it descends and approaches the pelvic floor. As a result, the chances of positive CRM and local recurrence increase.10 Neoadjuvant chemoradiation to downstage the tumour is particularly important in this group of patients with ultra-low tumours. It is also the policy of this author’s centre to routinely offer neoadjuvant chemoradiation for ultra-low rectal cancer. Therefore, the hypothesis proposed by Wong et al9 is reasonable and underscores the importance of CRM during preoperative assessment.
 
The modern high-resolution MRI allows assessment of several characteristics of rectal cancer including the depth of tumour invasion, CRM, regional lymph node status, and extramural vascular invasion. These are features with prognostic value and serve to guide a more selective approach in neoadjuvant therapy of rectal cancer. In parallel with advances in chemoradiation and surgery, optimal care for rectal cancer is sophisticated and involves contribution from several specialists including radiologists, oncologists, pathologists, and colorectal surgeons. It is important that we keep abreast of advances in this field and manage patients within a multidisciplinary setting.
 
References
1. Hong Kong Cancer Registry, Hospital Authority. Summary of cancer statistics in Hong Kong in 2011. Available from: http://www3.ha.org.hk/cancereg. Accessed Aug 2014.
2. Poon JT, Law WL. Laparoscopic resection for rectal cancer: a review. Ann Surg Oncol 2009;16:3038-47. CrossRef
3. Heald RJ, Moran BJ, Ryall RD, Sexton R, MacFarlane JK. Rectal cancer: the Basingstoke experience of total mesorectal excision, 1978-1997. Arch Surg 1998;133:894-9. CrossRef
4. van Gijn W, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol 2011;12:575-82. CrossRef
5. Maas M, Beets-Tan RG, Lambregts DM, et al. Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol 2011;29:4633-40. CrossRef
6. Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004;351:1731-40. CrossRef
7. Taylor FG, Quirke P, Heald RJ, et al. Preoperative magnetic resonance imaging assessment of circumferential resection margin predicts disease-free survival and local recurrence: 5-year follow-up results of the MERCURY study. J Clin Oncol 2014;32:34-43. CrossRef
8. Taylor FG, Quirke P, Heald RJ, et al. Preoperative high-resolution magnetic resonance imaging can identify good prognosis stage I, II, and III rectal cancer best managed by surgery alone: a prospective, multicenter, European study. Ann Surg 2011;253:711-9. CrossRef
9. Wong EM, Lai BM, Fung VK, et al. Limitation of radiological T3 subclassification of rectal cancer due to paucity of mesorectal fat in Chinese patients. Hong Kong Med J 2014;20:366-70.
10. West NP, Finan PJ, Anderin C, Lindholm J, Holm T, Quirke P. Evidence of the oncologic superiority of cylindrical abdominoperineal excision for low rectal cancer. J Clin Oncol 2008;26:3517-22. CrossRef

Treat the patient, not just the eye pressure

Hong Kong Med J 2014 Aug;20(4):272–3
DOI: 10.12809/hkmj144309
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
EDITORIAL
Treat the patient, not just the eye pressure
Dexter YL Leung, FRCS, FHKAM (Ophthalmology); Alvin KH Kwok, MD, PhD
Department of Ophthalmology, Hong Kong Sanatorium and Hospital, Happy Valley, Hong Kong
 
Corresponding author: Dr Alvin Kwok (alvinkwok@hksh.com)
 
 Full paper in PDF
Worldwide, glaucoma is regarded as one of the commonest causes of irreversible blindness.1 The global burden of glaucoma continues to rise: in 2010, at least 60.5 million people suffered from glaucoma, and by 2020, this is estimated to reach 79.6 million, of whom 11.2 million will be irreversibly blind in both eyes.1
 
Quality of life (QoL) includes dimensions such as physical health, mental health, general health perceptions, social functional status, and independence.2 It has been shown that vision is consistently regarded as one of its key determinants.3 In a chronic disease such as glaucoma, the impact on vision, and hence QoL is, naturally, a very important subject.
 
Traditionally, research in glaucoma focuses on outcome parameters important for the ophthalmologists such as intra-ocular pressure (IOP), vertical cup-to-disc ratio (CDR), visual field status, and optical coherence tomography parameters such as the mean retinal nerve fibre layer (RNFL) thickness. No doubt these are important to the patients, but are no more than abstract ideas to them. Patients are more likely to be interested in their QoL. Unfortunately, some of the treatment modalities in glaucoma, while successful in preserving the optic nerve function, may sometimes have side-effects, diluting the gain in QoL.4 Even more unfortunately, in the past, few major ophthalmic clinical trials included QoL as part of their study protocol. So, a new treatment modality can be hugely successful in lowering IOP, preserving CDR, visual field, mean RNFL thickness and vision, and yet result in an unacceptable drop in QoL in the long term. In the year 2010, the US Food and Drug Administration endorsed that QoL assessment be included in all glaucoma clinical trials.5
 
Broadly speaking, there are currently four major categories of validated QoL analysis questionnaires used for glaucoma patients: the general health-related, vision-specific, glaucoma-specific, and utility value assessments. They differ in their internal consistency (as indicated by their Cronbach’s alpha values), test-retest reliability, and correlation with severity of glaucoma. No matter what category of tools we choose, one unique challenge we face is that none of these validated QoL questionnaires is in Chinese (in fact, all are in English, thereby, creating a language barrier).
 
The study by Lee et al6 represents a nice attempt to address these issues. Firstly, the authors translated the Glaucoma Quality of Life–15 questionnaire (GQL-15) into traditional Chinese via a careful back-translation procedure. The questionnaire is a relatively easy-to-use, glaucoma-specific QoL tool addressing four aspects: (1) central and near vision; (2) peripheral vision; (3) dark adaptation and glare; and (4) outdoor mobility.
 
Secondly, they correlate this Chinese version of GQL-15 with a relatively new and important glaucoma clinical parameter, namely, the visual field index (VFI). First devised by Bengtsson and Heijl7 in 2008, VFI is automatically calculated using the newer Humphrey visual field analyser. Visual field index has been shown to reliably correlate with visual field loss from glaucoma, and be considerably less affected by visual loss as a result of concurrent cataract, which is also common in the same age-group of patients with glaucoma.7 Using VFI also allows the clinician to determine glaucoma disease progression (ie worsening) using a trend-based algorithm in addition to the traditional event-based algorithm. It has been demonstrated that trend-based determination of disease progression may be more robust than an event-based one, and incorporating both trend and event-based analyses can improve detection of glaucoma progression.8 Visual field index is increasingly being used in large clinical glaucoma trials and, clinically, is convenient to measure. The choice of studying the correlation between VFI and GQL-15 is a good way forward as currently there are few similar published data on this topic.
 
In this study,6 the authors found that a lower VFI correlated well with poorer GQL-15 scores and, hence, a lower QoL. The most problematic activities affecting QoL in these patients were “adjusting to bright lights”, “going from a light to a dark room or vice versa”, and “seeing at night”. While these difficulties may seem immediately obvious to the eye doctors, the findings may have greater implications to the architectural lighting design specialists. It is high time now for Hong Kong to have a more mature discussion on the design of the city’s exterior and interior lighting to facilitate the visually impaired citizens. Some of the suggested lighting engineering measures are, for example, plenty of floor lamps and table lamps in recreation and reading areas; usage of adjustable blinds, sheer curtains, or draperies for window coverings to allow adjustment of natural light; choice of brightly coloured vases and lamps near the furniture to make them easier to locate; elimination of hazards such as electrical cords in the pathway; avoiding waxing the floor; lighting the stairways clearly and uniformly; installation of grab bars; placing signs at eye level, with large lettering and braille signage according to guidelines, for example, from the Americans with Disabilities Act, etc.9 A concerted effort from all stakeholders of the society, from the Government to the architectural societies including the lighting specialists, to various blindness prevention organisations including the ophthalmologists, is needed to effect positive changes.
 
The ultimate goal of glaucoma treatment is to maximise QoL and patient satisfaction, not just creating a beautiful set of numerical figures in IOP/CDR/visual field/RNFL thickness. Addressing issues relating to QoL will allow both the clinicians and patients to re-orientate themselves towards a common realistic therapeutic programme, leading to a more harmonious partnership in care. So here is an old truth newly understood: we care for the patient as a human, not just for the parameters.
 
References
1. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol 2006;90:262-7. CrossRef
2. Felce D, Perry J. Quality of life: its definition and measurement. Res Dev Disabil 1995;16:51-74. CrossRef
3. Spaeth G, Walt J, Keener J. Evaluation of quality of life for patients with glaucoma. Am J Ophthalmol 2006;141(1 Suppl):S3-14. CrossRef
4. Leung DY, Tham CC. Management of bleb complications after trabeculectomy. Semin Ophthalmol 2013;28:144-56. CrossRef
5. Varma R, Richman EA, Ferris FL 3rd, Bressler NM. Use of patient-reported outcomes in medical product development: a report from the 2009 NEI/FDA Clinical Trial Endpoints Symposium. Invest Ophthalmol Vis Sci 2010;51:6095-103. CrossRef
6. Lee JW, Chan CW, Chan JC, Li Q, Lai JS. The association between clinical parameters and glaucoma-specific quality of life in Chinese primary open-angle glaucoma patients. Hong Kong Med J 2014;20:274-8. CrossRef
7. Bengtsson B, Heijl A. A visual field index for calculation of glaucoma rate of progression. Am J Ophthalmol 2008;145:343-53. CrossRef
8. Medeiros FA, Weinreb RN, Moore G, Liebmann JM, Girkin CA, Zangwill LM. Integrating event- and trend-based analyses to improve detection of glaucomatous visual field progression. Ophthalmology 2012;119:458-67. CrossRef
9. Information and Technical Assistance on the Americans with Disabilities Act, Civil Rights Division, United States Department of Justice. Available from: http://www.ada.gov/2010_regs.htm. Accessed 1 Jun 2014.

Comparison is beyond IPASS and OPTIMAL

Hong Kong Med J 2014;20:176–7 | Number 3, June 2014
DOI: 10.12809/hkmj144267
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
EDITORIAL
Comparison is beyond IPASS and OPTIMAL
KC Lam, FHKAM (Medicine)1; Tony SK Mok, FHKCP, FHKAM (Medicine)2
1 Department of Clinical Oncology, Prince of Wales Hospital, Shatin, Hong Kong
2 Department of Clinical Oncology, The Chinese University of Hong Kong, Shatin, Hong Kong
 
Corresponding author: Dr KC Lam (kc_lam@clo.cuhk.edu.hk)
Now that first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) is recognised as a standard therapy for non–small-cell lung cancer (NSCLC) with activating mutations,1 2 3 4 5 6 7 it is only natural for some of us to ask which TKI is the best. In the absence of a direct head-to-head randomised controlled study, Lee et al8 used an indirect comparison method to compare the efficacy and cost-effectiveness of gefitinib and erlotinib, results of which are published in this issue. The authors concluded that erlotinib has better efficacy and is more cost-effective than gefitinib.8 Is this a trustworthy conclusion?
 
For reason that is not entirely clear to us, authors chose to use data from only the OPTIMAL and IPASS studies. Truth is that there are four randomised studies on gefitinib (IPASS, FIRST-SIGNAL, NEJ-002, and WJTOG 345) and three randomised studies on erlotinib (OPTIMAL, EURTAC, and ENSURE) in patients with activating EGFR mutation–positive NSCLC. The authors excluded EURTAC study from the comparison because of the differences in baseline demographic data and ethnicity. Similar to IPASS, EURTAC is a registration study using stringent criteria for documentation of treatment outcomes and toxicity. The OPTIMAL study was not considered a registration study by the China Food and Drug Administration, and that was exactly the reason for the replication of OPTIMAL study (ENSURE study) in China. Grade 3 or above skin rash rate was higher in the EURTAC study (13%) as compared with IPASS study (3.1%), and this is a fact that should not be ignored. The median progression-free survival (PFS) and hazard ratio were comparable between EURTAC and IPASS and, again, this fact was ignored. Lee et al8 should incorporate data from more relevant clinical trials into the indirect comparison to provide a non-biased estimate of the true treatment effect. As erlotinib is slightly more expensive than gefitinib in the Hong Kong public health care system, it will be unrealistic to conclude a better cost-effectiveness if the two drugs were shown to have similar efficacy in an honest manner.
 
Kim et al9 conducted a prospective open-label randomised non-comparative parallel study in a single Korean hospital to evaluate the efficacy of erlotinib and gefitinib in those EGFR mutation–positive NSCLC patients or patients with at least two out of three clinical factors associated with higher incidence of EGFR mutations who failed platinum-based chemotherapy. In this exploratory comparison, there were no statistically significant differences in response rate and median PFS between the two drugs. More treatment-related grade-3 or -4 adverse events were observed with erlotinib versus gefitinib (12.4% vs 4.2%). Wu et al10 conducted a retrospective study to evaluate the difference in efficacy between erlotinib and gefitinib in Taiwanese patients with advanced-stage EGFR mutation–positive NSCLC. They also found no statistically significant difference in response rate and PFS between the two drugs. Lim et al11 performed a retrospective review to examine the treatment outcomes with two EGFR TKIs with a match-pair case-control study design. Again, there were no statistically significant differences in response rates, PFS, and overall survival between the two drugs. An ongoing prospective randomised trial in China compares erlotinib with gefitinib in NSCLC patients harbouring EGFR exon 21 mutation. This will be the only true head-to-head comparison between gefitinib and erlotinib in this setting.
 
While we argue about which is a better EGFR TKI, treatment paradigm is shifting to second and third generations of EGFR TKIs. Afatinib, an irreversible pan-HER inhibitor, has been proven to be superior to standard platinum-based chemotherapy.12 LUX–Lung 7 trial, a randomised phase IIb study comparing afatinib to gefitinib in EGFR mutation–positive NSCLC, is completed and results are pending. Furthermore, ARCHER 1050 will be the first randomised phase III study comparing dacomitinib with gefitinib in patients with either exon 19 or 21 mutations. Phase I studies on third-generation EGFR TKIs including AZ9291 and CO1686 have also reported high tumour response rate in patients with resistant T790M mutation. Its role as first-line EGFR TKI remains to be explored.
 
Treatment of advanced-stage lung cancer is rapidly evolving. Instead of asking the question of which is a better EGFR TKI, perhaps we should focus on how to improve outcomes for our future patients.
 
References
1. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009;361:947-57. CrossRef
2. Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010;362:2380-8. CrossRef
3. Mitsudomi T, Morita S, Yatabe Y, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG345): an open label, randomised phase 3 trial. Lancet Oncol 2010;11:121-8. CrossRef
4. Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 2011;12:735-42. CrossRef
5. Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 2012;13:239-46. CrossRef
6. Han JY, Park K, Kim SW, et al. First-SIGNAL: first-line single-agent iressa versus gemcitabine and cisplatin trial in never-smokers with adenocarcinoma of the lung. J Clin Oncol 2012;30:1122-8. CrossRef
7. Wu YL, Zhou C, Wu G, et al. Quality of Life (QoL) analysis from ENSURE, a phase 3, open-label study of first-line erlotinib versus gemcitabine/cisplatin (gp) in Asian patients with EGFR mutation-positive NSCLC. J Thorac Oncol 2014;9:7S-52S.
8. Lee VW, Schwander B, Lee VH. Effectiveness and cost-effectiveness of erlotinib versus gefitinib in first-line treatment of epidermal growth factor receptor–activating mutation-positive non–small-cell lung cancer patients in Hong Kong. Hong Kong Med J 2014;20:178-86.
9. Kim ST, Uhm JE, Lee J, et al. Randomized phase II study of gefitinib versus erlotinib in patients with advanced non-small cell lung cancer who failed pervious chemotherapy. Lung Cancer 2012;75:82-8. CrossRef
10. Wu WS, Chen YM, Tsai CM, et al. Erlotinib has better efficacy than gefitinib in adenocarcinoma patients without EGFR-activating mutations, but similar efficacy in patients with EGFR-activating mutations. Exp Ther Med 2012;3:207-13.
11. Lim SH, Lee JY, Sun JM, et al. Comparison of clinical outcome between gefitinib and erlotinib treatment in patients with non-small cell lung cancer harbouring an epidermal growth factor receptor exon 19 or exon 21 mutations [abstract]. J Clin Oncol 2013;31 Suppl:e19051.
12. Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 2013;31:3327-34. CrossRef

Benefits of early detection and treatment of human immunodeficiency virus infections

ABSTRACT
Hong Kong Med J 2013;19:472–3 | Number 6, December 2013
DOI: 10.12809/hkmj134162
EDITORIAL
Benefits of early detection and treatment of human immunodeficiency virus infections
SS Lee
Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong,(c/o) 2/F Postgraduate Education Centre, Prince of Wales Hospital, Shatin, Hong Kong
 
 
No abstract available.
 
View this abstract indexed in MEDLINE:
 

Raising the ante in anti-counterfeit drug legislation

ABSTRACT
Hong Kong Med J 2013;19:284–5 | Number 4, August 2013
DOI: 10.12809/hkmj134089
EDITORIAL
Raising the ante in anti-counterfeit drug legislation
Alan J Worsley, Ian CK Wong
Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 2/F, 21 Sassoon Road, Laboratory Block, Faculty of Medicine Building, Hong Kong
 
 
No abstract available.
 
View this abstract indexed in MEDLINE:
 

Triage in accident and emergency departments and possible outlets for patients with less-than-urgent medical problems

ABSTRACT
Hong Kong Med J 2013;19:196–7 | Number 3, June 2013
EDITORIAL
Triage in accident and emergency departments and possible outlets for patients with less-than-urgent medical problems
HF Ho
Accident and Emergency Department, Queen Elizabeth Hospital, Jordan, Hong Kong
 
 
No abstract available.
 
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